In the two years and five manned flights following the suborbital flight of Alan B. Shepard, Jr., in May 1961, the American space program underwent considerable change. Shortly after Shepard's flight, NASA responded to President Kennedy's call for a manned lunar landing before 1970 with its manned lunar landing program, which included two major series of manned flights, Projects Gemini and Apollo. By the time Gordon Cooper made the last Mercury flight on May 15,1963, NASA's manned space program had changed from a small-scale project with limited objectives into a large-scale, multifaceted program representing a major national effort.1
This expanded program posed major challenges for NASA's biomedical staff. The Mercury flights carried a single man into low orbit, and the flights were no longer than one day. In Gemini and Apollo, life systems would have to accommodate two and three men for up to two weeks. The space capsule would have to provide protection against radiation and higher rates of acceleration sustained for longer periods than experienced during Mercury. Finally, longer flights would require attention to personal comfort, food, waste management, sleep, and physical mobility. Other concerns included prolonged exposure to weightlessness, 100 percent oxygen atmosphere' atmospheric contaminants, physical confinement, and altered circadian rhythms. While the Mercury flights gave some confidence in man's ability to survive and perform effectively in space, questions remained about long-duration flights. 2
BIOMEDICAL LEGACY OF PROJECT MERCURY
From a biomedical standpoint, Project Mercury was an unqualified success Stanley White, head of aeromedical consultants, observed:
 The astronaut learns and adjusts quickly to his environment His body senses of vision, hearing, smell, and touch appear to be unchanged. His kinesthetic sense is present. Being inverted or flying backward has been described as being surprising but of no consequence to the astronaut Motor sensations appear unchanged. Eating, drinking, and urination appear normal the performance of flight tasks by the astronauts has been highly successful on each flight gastrointestinal absorption and renal excretion have shown results comparable to preflight controls In addition, no positive physical or significant biochemical change has been measured in the preflight-postflight studies.3
Dr. Charles Berry, from 1963 the director of Center Medical Operations at the Manned Spaceflight Center and the astronauts' physician, added that the Mercury flights revealed that, in spite of 'numerous stresses," the spaceflight environment produced no unmanageable physiological overload," and the missions indicated that weightlessness and acceleration forces would be of little consequence in subsequent missions.4
Project Mercury had two primary biomedical objectives. The first was to provide the medical support necessary to enable man to fly safely in missions that were not to exceed two days in duration. This objective was met through astronaut selection and training procedures, the environmental control system, and medical maintenance and monitoring programs. No significant problems related to astronaut health and performance, life systems, or medical operations arose during any of the Mercury flights.
The second objective was to investigate human physiological and performance reactions to spaceflight, which would contribute to planning future manned missions. Specifically, physicians wanted to know how long man can be exposed to the spaceflight environment without significant physiological or performance decrements, the causes of any observed changes, and preventive measures or treatments that should be used to counter any decrements.5 Since Project Mercury had no provision for controlled inflight biomedical research or experimentation, the required data were obtained through medical evaluations before, during, and after fIight.
Procedures for obtaining biomedical data changed little during the Mercury series. Preflight evaluations were used to determine the readiness for flight and to obtain medical data for comparison with postflight data. Three to five days before each launch, specialists in neurology, opthalmology, aviation medicine, psychiatry, and radiology conducted thorough physical examinations that included electrocardiograms, audiograms, electroencephalograms, biochemical studies of blood and urine, and tests to assess the condition of the astronaut's vestibular apparatus (control of balance and orientation by the inner ear). Results were compared with the astronaut's medical history, including data from simulations and centrifuge runs. On the day of launch, physicians made  general assessments of the astronaut s mental and emotional state, measured his vital signs (pulse, blood pressure, oral temperature, and weight), and checked for changes in lungs, eyes, ears, nose, or throat since the previous examination. The same checks were repeated after the fIight.6
Inflight monitoring was performed to keep mission control apprised of the medical status of the astronaut and also to provide medical data of research interest Since Mercury physicians doubted the reliability of bioinstrumentation, they relied primarily on voice assessments and the astronaut's own personal observations for inflight medical evaluations. At the same time, attempts were made to improve the instruments, and bioinstrumentation was the only aspect of medical operations that underwent significant change as the Mercury missions progressed. The initial plan, which was followed during the suborbital flights of Shepard and Virgil Grissom, involved use of three bioinstruments: an electrode sensor applied to the chest to produce electrocardiograms, a respiration sensor mounted within a microphone in the helmet, and a rectal thermistor to measure body temperature. For the orbital flights, a decision was made to develop instrumentation for measuring blood pressure.7
At the very beginning of the Mercury project, Stanley White had hoped to measure blood pressure in flight, but acceptable instruments were not to be found. Available hardware was either not compatible with the other data links or could not pass the qualification testing." Consequently, plans for blood pressure testing were "tabled temporarily," though arrangements were made to review progress" at six-month intervals.8 As events unfolded, the interest of biomedical spokesmen outside NASA forced an accelerated effort to develop the instrumentation that became known as the blood pressure measurement system (BPMS).
Before Alan Shepard's flight, some biomedical scientists had expressed concern over the rapid heart rates recorded during flights of the X-15 experimental aircraft and during astronauts' runs on the Johnsville centrifuge These concerns led to an investigation by the President's Science Advisory Committee, which concluded that medical preparations for Mercury were adequate. Nevertheless, some investigators were disturbed by the heart rates (180+ beats per minute) and the absence of instruments for measuring blood pressure. Fearing that these concerns might cause a delay in the Mercury program, Space Task Group Director Robert Gilruth directed the Life Systems team to devise a reliable instrument for measuring blood pressure before the first manned orbital flight.9
The BPMS posed a major bioengineering challenge because the Pressure suit and space capsule systems were not designed to accommodate such an instrument. Designing the pressure cuff itself was not a significant problem as it could follow the principles that govern the  sphygmomanometer, an inflatable cuff that records systolic and diastolic pressure in the brachial artery of the left arm and is used to measure blood pressure under normal circumstances. The chief difference would be that a microphone, rather than a physician or nurse, would monitor the sounds.
A number of complications were involved in adapting the pressure cuff to Mercury systems: its effect on movement of the astronaut s arm, compatibility of the inflated cuff with the pressure suit, and addition of new leads into the telemetry channels without unduly complicating the electrical systems. In addition, physicians and engineers had to establish the accuracy of an instrument that is normally used on a passive subject in a quiet environment, but would now have to be adapted to work on an active subject in a noisy environment.10
Through a crash program, the BPMS was ready for the first American manned orbital flight. However, the instrument did not work because the astronaut, burdened with numerous inflight tasks, failed to turn it on. An automatic BPMS installed for the next flight was not accurately calibrated. Accurate readings depended on calibration matched to the baseline values for the individual astronaut. Exact calibrations were made for the last two Mercury missions, and excellent readings were obtained.11
As the flights progressed, a minor change was made in the method for measuring body temperature. During the first five flights body temperature had been measured rectally. Given the length of the final mission, planners decided that oral measurements should be used This involved no changes in the electronic leads or telemetry channels; the thermistor was simply moved to an earmuff.12
In the four orbital missions, an effort was made to evaluate man s ability to absorb food in the weightless state. Toward these ends, each astronaut ate a cube of xylose (a sugar) during weightlessness. This test revealed that the astronauts could eat in flight, but that great care had to be taken to avoid crumbling the food. Xylose is quickly absorbed and excreted, and it was expected that urine samples would provide a measure of absorption rates during the weightless state. The test proved invalid for the first two flights, since it was impossible to separate the preingestion urine samples from those obtained after ingestion. Minor engineering changes made such separation possible in the final two flights, and resulting data demonstrated that the space environment does not interfere with intestinal absorption of food.13
Overall, the Mercury missions increased the physicians confidence in man's physiological and psychological capabilities for long-duration spaceflight. However, some physiological abnormalities were revealed first, in all four orbital flights the astronauts experienced dehydration; Unusual amounts of water were needed and urine output was higher than anticipated. This was especially evident in the 10-hour flight of Walter  Schirra and the 1-day flight of Gordon Cooper. However, physicians were uncertain whether dehydration was an effect of weightlessness or a consequence of the artificial environment. White, for example, was convinced that it resulted from inadequate control of the suit environment within the air-conditioning system, yet he and his colleagues recognized that other factors might have contributed to the problem.14
A second and potentially more serious abnormality appeared immediately after the Schirra and Cooper flights. When they first stood up after leaving the recovery craft, the astronauts experienced orthostatic hypotension This syndrome involves fainting, or near-fainting, and is brought on by an abrupt drop in blood pressure and a sharp increase in pulse rate as the cardiovascular system fails to provide sufficient blood to the brain. Here again, it was impossible for physicians to identify with confidence the predisposing cause or causes of this condition. While unwilling to rule out spaceflight stress factors, they believed that the cause was prolonged physical immobility, since the syndrome had often been observed in persons who experienced prolonged bed rest. Nevertheless, the cardiovascular system would require close investigation during long-duration spacefIight. 15
Physicians were also troubled by some minor indications of potential physiological and performance degradation. Cooper was so fatigued, apparently because of lack of sleep, that he required dextroamphetamine sulfate before reentry.16 Lack of sleep could impair performance and the Gemini and Apollo missions would require far more crew involvement and control of the mission and spacecraft than was needed in Mercury Fatigue would be a special concern during reentry.
Finally, postflight analyses revealed imbalances in blood and urine electrolytes (the chemical ions normally present). Calcium and phosphorus, the principal elements in the skeletal and dental systems, were present in unusually high concentrations. This indicated some demineralization of the bones and possibly the teeth and required further investigation.17
Thus, despite the success of Project Mercury, NASA s physicians faced the Gemini and Apollo missions with some apprehension. First, the anomalies just described indicated a need for more precise information on cardiovascular function, electrolyte changes, and performance decrements. Charles Berry convinced NASA management to make two changes in the projected Gemini program, increasing inflight experiments (perform controlled studies) related to the abnormalities observed during Mercury, and reducing the first manned Gemini flight from the planned eight-day mission. NASA changed the first manned Gemini flight to a four-day mission. 18
There remained the need for more reliable bioinstrumentation. White Concluded from the Mercury experience that the frequency of direct voice  contact with astronauts would decrease in proportion to the length of the missions, and bioinstrument reading would become the primary means of evaluating inflight medical status. Since this would depend on periodic transmissions, he foresaw an associated requirement for improved methods of data handling and storage.19
Finally, physicians were concerned about new or magnified stress factors: longer exposure to acceleration forces, radiation fields, and the natural and artificial stresses of the spaceflight environment. These factors warranted a continuation of the incremental approach to qualification of man for spaceflight; improved (and approved) methods for gathering, storing, and analyzing biomedical data; and provision for inflight biomedical experiments. 20
BIOMEDICAL REQUIREMENTS FOR MANNED LUNAR LANDING
NASA had been studying the technical requirements for a manned mission to the Moon since 1959. By late 1961 the means of getting there had been selected: lunar orbit rendezvous, in which a compound spacecraft orbiting the Moon would separate, with one component (two men) going to the surface while the other (one man) remained in orbit. Later, part of the landing vehicle would rejoin the orbiting vehicle, after which the crew would return to the Earth. This scheme was selected over the direct flight of a single vehicle from the Earth to the Moon because the problems of rendezvous in space were considered easier to overcome than those of building the large launch vehicles (Earth and lunar) required for the more direct operation. Orbital rendezvous nevertheless posed significant engineering and operational challenges, not the least of which would be the need for the astronauts to control spacecraft maneuvers.
Project Gemini was authorized in 1962 to develop the equipment and procedures needed to rendezvous in orbit. It became an active project in 1963 and, though viewed as part of the lunar effort, was managed separately from Apollo. By the time Gemini became operational it had the specific objective of demonstrating that man could operate in space for up to 14 days, the time required for a lunar journey.21 From a biomedical standpoint, Gemini was the key to the manned lunar program, since most of the biomedical stresses and variables that would affect the Apollo crews could be evaluated during the Gemini missions. Gemini and Apollo would differ in engineering systems, launch vehicles, crew size, and flight plans, but medical operations would be essentially the same, and stresses experienced by the Apollo crews, though somewhat different, in the main, would be represented by those experienced by the Gemini crews.
The critical variables that physicians anticipated for Gemini (and Apollo) included acceleration, weightlessness, radiation, space capsule  environment, food and water, waste management, and performance factors (isolation and confinement, sleep, man-machine integration). Each was considered significant because of the mission configuration (higher orbits, longer exposure to acceleration forces), the mission duration, and the possibility that two or more of these variables could interact to degrade physiology and performance
The Mercury flights had revealed no decrement in physiology or performance that could be attributed to the acceleration forces experienced during launch and reentry While the peak acceleration and deceleration forces anticipated for Gemini would not exceed those of the Mercury flights, they would be maintained longer to propel the capsule to the higher orbits, and due to the higher speed at reentry, would necessitate a longer period of deceleration. 22 Physicians were most concerned by the combined stress of the abrupt shifts from sustained launch acceleration to weightlessness and from weightlessness to sustained deceleration during reentry. Long before the first Mercury flight, physicians had been disturbed by the implications of the theoretical Henry-Gauer effect-that is, inability of the cardiovascular system to respond quickly to such abrupt shifts, causing astronauts serious trouble during reentry.
This syndrome had not appeared during Mercury, but then exposure to weightlessness had been relatively brief. NASA physicians feared that, for Gemini, longer periods of weightlessness could subject the cardiovascular system to serious stress in the launch and reentry phases. They also suspected this cardiovascular stress could contribute to more severe orthostatic hypotension when the returned astronauts resumed an upright position. 23 Medical preparations for these contingencies included the introduction of cardiovascular conditioning routines in the astronaut training program, expanded research into the cardiovascular effects of prolonged bed rest, efforts to develop bioinstrumentation that would function during launch and reentry, and design studies to improve the couch, restraint' and escape equipment. Physicians also devised inflight experiments to obtain more precise data on cardiovascular response to spaceflight. These were to be performed on all flights up to 14 days, but were considered most critical in the 4- and 8-day flights. 24
Three medical experiments were planned to measure cardiovascular performance. A cardiovascular conditioning experiment (later designated M-1) was designed to test a procedure for minimizing the reduction in blood flow during weightlessness. A pair of pneumatic cuffs on the lower legs, inflated to 70 to 75 millimeters of mercury for two minutes out of  every six, should increase venous pressure above the cuffs, thereby reducing "pooling of blood in the extremities" and increasing "the effective circulating blood volume" following exit from weightlessness. The cuffs were to be tested during controlled studies on subjects immersed in water for extended periods before the experiment was flown. 25
A second experiment with an inflight exercise was intended both to measure cardiac function and to reduce the effect of prolonged immobility on cardiovascular performance. The exerciser consisted of two bungee cords connected to a handgrip and a loop for the feet At prescribed intervals, the astronaut would place his feet in the foot loop and pull upward on the handgrip. Full extension of the handle (26.4 centimeters) would require 70 pounds of force During exercise periods, heart and respiration rates and blood pressure would be recorded on magnetic tape and also telemetered to ground control. 26
The third cardiovascular experiment was a combined electrocardiogram (electrical heart activity) and phonocardiogram (mechanical heart activity). A sensor for measuring electrical output and a transducer for measuring vibrations caused by heartbeats would be affixed to the astronaut's chest. Together, the instruments would provide data on cardiac function in flight and report the medical status of the astronaut from launch to recovery. 27
Development of these experiments would require close coordination between physicians and other members of the spaceflight team. Major responsibility for development of bioinstrumentation and integration of instruments into spacecraft systems rested with the Life Systems (later Crew Systems) Division of the Manned Spacecraft Center. Interaction with this group was not expected to cause any difficulties, since the physicians and engineers in that division had been working together closely and effectively from the beginning of the space program. The real problem would be the reluctance of the astronauts to cooperate in the experiments. Besides the inconvenience and discomfort involved, the astronauts were concerned that the bioinstruments would uncover information that could lead to their being grounded. This was a continuous source of tension throughout the manned program, as the astronauts recalled how Deke Slayton, one of the original seven astronauts, had been grounded after it was found that he had a minor (to the astronauts) arrhythmia of the heart. The astronauts' cooperation was gained through diplomacy, tact, and appeals to higher authority from Charles Berry. 28
The data from Mercury, though crude from a scientific perspective, suggested that the human body adapts to the weightless state and that man  can perform effectively in null gravity. Physicians were more worried about the problem of readaptation to the Earth's gravity. They were concerned about changes in the cardiovascular system in particular, but also about changes in body fluid electrolyte balance, body fluid volume, and vestibular function. Consequently, they were anxious to investigate the physiological changes that occur during prolonged weightlessness and to measure the time required to return to normal.
Since weightlessness could not be effectively simulated on the ground, inflight experiments were the only means of investigating these problems. Toward this end, Berry and Lawrence Dietlein, the medical research director at the Manned Spaceflight Center, convinced NASA management to include medical experiments during the 8- and 14-day flights. The desired experiments included studies of the cardiovascular system, fluid electrolytes, fluid volume, bone demineralization, and vestibular function.
Three experiments were developed for the study of electrolyte changes. One (eventually designated M-5) involved preflight and postflight biochemical analyses of blood and urine and analysis of urine samples collected in flight (collection of blood samples in flight was considered impractical). The preflight-postflight analyses were intended to identify changes in the body fluid electrolytes that would indicate the "physiological cost to the crewman in maintaining a given level of performance during space flight." These analyses were also expected to reveal the length of time required for the astronaut's systems to return to normal, as blood and urine samples would be drawn at prescribed intervals during the 72 hours after the return to the Earth. The urine samples collected in flight would also be analyzed for electrolyte balance, to provide some indication of the physiological changes that occur during weightlessness, and their volume would be compared with fluid intake to help physicians understand the dehydration experienced by Mercury astronauts. 29
Two other experiments to measure electrolyte balance as a function of changes in the muscular and skeletal systems were intended to assess "the effect of prolonged weightlessness and immobilization" and the length of time required for these effects to disappear. Experiment M-6, a study of bone demineralization, involved making a determination of changes in the density of two bones (one in the left foot, the other in the left hand) through analysis of x-rays taken at specified intervals before and after flight. 30 M-7 would be a biochemical analysis of the urine samples collected before, during, and after flight. Excreted calcium and nitrogen Would be taken as indications of demineralization of bones and muscles. Controls for this experiment would be urine samples from subjects undergoing prolonged bed rest and samples from the individual astronauts before flight.31
 Because the physicians were as much concerned with the astronauts performance as with their physiology, two experiments were planned to investigate factors that might affect performance. Experiment M-8 would be an analysis of sleep patterns in flight. Electroencephalograms would be taken during preflight periods of sleep and used as baseline values.32 In experiment M-9 the performance of the otoliths (the part of the inner ear most directly involved in balance and orientation) would be assessed by determining the ability of the astronauts to "estimate horizontality" in the absence of visual and gravitational clues. This would help predict the possible effect of prolonged weightlessness on otolith function.33
Here again, close cooperation and coordination-as well as tact and diplomacy-were needed to ensure the integration of experiments with space capsule systems and the cooperation of the astronauts. The sleep study in particular was anathema to some of the astronauts, who feared that the electroencephalograms were really intended to measure their psychological reactions. However, this experiment was planned for the 14-day mission, which was to be commanded by Frank Borman, who recognized the value of medical experiments and supported the medical program. 34
The Gemini and Apollo astronauts would encounter radiation from several sources: the Van Allen belt, outer space, and solar flares. Protecting them against radiation was primarily a problem for physical scientists and engineers, since it involved the development of shielding that would provide adequate protection, yet not impose severe weight penalties or be incompatible with spacesuit and capsule design. Biomedical personnel did have a role to play, however.
Before shielding could be developed, engineers required specifications on maximum permissible exposure (cumulated dose, intensity times duration) to the different types of radiation. NASA's biomedical personnel planned to approach this problem in two ways. First, in ground-based investigations different types of tissue would be exposed to radiation to determine how much could be absorbed before there was evidence of deterioration in the tissue mass or changes in the composition of the  chromosomes Second, tissue would be flown into the Van Allen belt and changes would be noted. Subsequently, engineers would test different shielding materials to identify those which kept radiation beneath the maximum permissible level. In addition, mission planners intended to include dosimeters (instruments to measure radiation levels) on all flights to warn the astronauts of shielding failure Physicians also hoped to identify drugs that would either provide protection against radiation or reduce the effects of exposure.35
SPACE CAPSULE ENVIRONMENT
Like radiation protection, the environmental control system (the term encompassed capsule life support systems and spacesuits) was primarily a matter of concern to engineers. Physicians had to provide the specifications necessary to ensure integration of biomedical instrumentation into capsule and suit systems, maintenance of a 100 percent oxygen atmosphere at a pressure range of 3.5 to 5.0 pounds per square inch, and maintenance of suit and cabin temperature and humidity levels within comfort and health limits.36
Physicians were concerned, however, with matters associated with the environmental control system, specifically possible physiological and performance decrements resulting from prolonged exposure to the space capsule environment. The astronauts would be breathing 100 percent oxygen for up to 14 days, and the long-term effects were unknown. Ground-based studies had revealed some changes in blood volume and composition in subjects exposed to comparable environments for prolonged periods, and such changes could have serious effects during long flights. Discovering such decrements in the early Gemini flights would allow time to devise effective countermeasures before the problem became serious.37
Another concern was the possibility of exposure to atmospheric toxins. The corrosive products of oxidation (especially the oxidation of heavy metals such as mercury, lead, and copper) can be highly toxic. Natural oxidation does not normally pose a health hazard because oxygen is only 20 percent of atmospheric air and the corrosion products quickly disperse. However, in the sealed environment of the space capsule with its 100 percent oxygen atmosphere, the oxidation rate would increase dramatically and the corrosion products (toxics) would quickly become highly concentrated.
Besides the oxidation of capsule materials, the other obvious source of atmospheric toxins was carbon dioxide from respiration. This was not expected to be a significant problem, since the Mercury experience had shown that the carbon dioxide could be removed by drawing it through a  filter containing lithium hydroxide; the two chemicals interact, producing water and lithium carbonate. 38
The identification of toxic corrosion products was a far more complex problem, since virtually every substance used in the construction of the space capsule could produce a toxic contaminant. For example, it was necessary to remove all the name plates from the interior of the Gemini capsule because the adhesive used to attach them combined chemically with the name plate and created a toxic product. The only clue to this was a slightly objectionable odor in the capsule. Physicians and chemical engineers had to identify potentially toxic substances and determine the levels at which they pose health hazards to humans. For this reason, toxicology became an area of major biomedical research interest.39
FOOD AND WATER
Longer flights would require larger quantities of food and water, and here again, physicians had to work closely with design engineers and mis.....
 .....sion planners. From a medical standpoint, the astronauts required sufficient food and water to ensure optimum performance. The food had to be nourishing, produce no undesirable physiological effects (nausea, diarrhea, or flatus), and have a composition so that it would be ingestible in flight. The engineers were interested in storing the food and water in as small a space as possible. Weights were also important.
The responsibility of physicians and biomedical scientists in this area was to establish precise metabolic requirements for men who would be largely immobile, but who had to be fully alert and physically capable of exerting the energy required for extravehicular activities. Physicians planned to develop preliminary specifications through metabolic studies on two different types of subject: those confined to prolonged bed rest and those made to perform strenuous work while immersed in water. The exact metabolic costs would be determined by giving the subjects carefully measured and analyzed quantities of food and water and quantitatively analyzing their urine and feces. These studies would provide only general guidelines; more precise information would have to wait until the first Gemini flights. Some of the experiments already described would yield the precise metabolic data needed to plan the food and water requirements of the later Gemini and the Apollo missions. In addition, the Gemini flights would provide an opportunity to test and evaluate different foods.40
WASTE MANAGEMENT AND PERSONAL HYGIENE
Waste management and hygiene were not problems during Project Mercury because of the short mission durations. Fecal elimination was avoided by placing the astronauts on a low-residue diet for 7 to 10 days before launch. Provision for urination was necessary, but the weight and volume of urine collected would not affect vehicle design or weight. Likewise, personal hygiene was not an issue since the astronauts would return before soil on the body could lead to discomfort. In the longer Gemini and Apollo flights, defecation could not be avoided, the amount of urine collected would be quite large, and uncleanliness would be both psychologically troublesome and physically uncomfortable.
The issues in this area were fundamentally engineering ones and did not require much in the way of medical input. Engineers needed some information in order to predict the amount of fecal and urine output, and such information would become available from the metabolic studies and blood and urine analyses. They also needed to know how much provision should be made for hygiene in flight-for example, how often, if at all, the astronauts would have to wash to avoid skin ailments. With these exceptions, waste management was strictly an engineering problem.41
Physicians and mission planners were concerned with pilot performance in long-duration flight, since the astronauts would be directly involved in Spacecraft maneuvers during the Gemini and Apollo missions. There appeared to be four factors that could interfere with pilot performance: disorientation resulting from unanticipated effects of acceleration and Weightlessness on vestibular function, serious dysfunction of a Physiological system due to acceleration and weightlessness, psychological reactions to isolation and confinement, and inflight illness. The first two of these have been discussed in other sections of this chapter.
 NASA's physicians recognized that psychological dysfunction due to prolonged confinement was possible, but they doubted that it was probable. Psychological testing and psychiatric evaluation had been critical parts of the astronaut selection process, and anyone with indications of emotional or mental weakness had been screened out. These tests included questions that were used in evaluating candidates for submarine duty Moreover, physicians considered the test pilot background of the astronauts to be a reliable guarantee of their psychological fitness Nonetheless, NASA sponsored some research in this area, including studies of airmen confined singly and in groups for periods up to 90 days and sociological studies of small-group interactions. None of this research yielded data of significance to the Gemini and Apollo missions.42
Inflight illness was a serious concern; it could be disastrous on flights that left Earth orbit because the spacecraft would have to loop around the Moon before returning to the Earth. No Mercury astronaut had experienced any significant inflight illness; but motion sickness had been a serious problem in Russian flights. In addition, many possible ailments could arise, and physicians insisted that the astronauts be able to treat the symptoms of the most likely ones. The medical kit on Gemini included 12 drugs for treatment of motion sickness, extreme fatigue, aches and inflammations, diarrhea, nasal and sinus congestion, irritation and inflammation of the eyes, bacterial infection, and severe pain. The kit also included creams for treating skin irritations and tapes and bandages for cuts.43
In their approach to these various challenges, NASA's physicians made no effort to investigate the assorted problems through systematic animal research. Many biomedical scientists outside NASA criticized this approach. In response to outside scientists' complaints, two monkeys had been flown in Mercury capsules prior to John Glenn's flight, but NASA rejected suggestions of an animal program in support of Gemini and Apollo. Although many scientists outside NASA found it difficult to understand this position, it made good sense to NASA's planners, engineers, and physicians.
NASA management opposed making animal research an adjunct to the manned program. President Kennedy had set an arbitrary deadline for a lunar landing and since there was no evidence that the incremental approach to qualifying man for spaceflight created unacceptable levels of risk, management saw no reason to further complicate the program. They were not opposed to animal research per se, but felt that such research should be conducted solely for scientific purposes and should be separate from the manned program.44
 NASA's physicians opposed making the manned program dependent on animal research, in part, due to reflection of their background and experience; with few exceptions, the biomedical personnel at the Manned spaceflight Center were either career military physicians on temporary assignment to NASA or civilian physicians who had come to NASA after Separation or retirement from military service. Their flight medicine orientation favored using man as the measure of man's response to flight and viewed animal research as useful only in studying phenomena observed during manned flights.45
Animal research was important in the overall space program, however. Project Biosatellite, started in 1963, was projected to be a series of unmanned flights in which increasingly complex organisms would be flown for periods of up to 30 days. Although it was a scientific endeavor, it was also justified in some agency and outside scientific circles as having the ability of contributing information of value for manned flights. The Biosatellite program had three flights between December 1966 and June 1969. The first and last flights were judged unsuccessful. The second, a two-day flight in September 1967, provided some data on cells, plants, and animals.
Ames Research Center was also developing programs in basic biological and medical research that involved animals rather than humans. Ames life scientists hoped to link their research programs to the manned program, but met with little success.47 Even at the Manned Spacecraft Center the medical research group established an animal program, but with the understanding that the animals would be used only for backup studies or for research that could not be conducted easily or safely on humans.48
BIOMEDICINE AND ADVANCED MANNED SPACEFLIGHT
By 1963, both NASA and the Air Force were looking beyond Apollo. The Air Force was under pressure from Secretary of Defense Robert McNamara to cancel its only active manned space program, Dyna-Soar, and Air Force officials were seeking some type of manned program that would not duplicate NASA's efforts but would keep the Air Force involved in space activities. By early 1964, the Air Force had tentative approval to develop a program leading toward a Manned Orbiting Laboratory (MOL). 49
NASA no longer had any need to engage in active competition with the Air Force' but agency officials did not want to be unprepared when the time came to push for authorization to conduct a post-Apollo manned Program During the year after the final Mercury flight, several planning groups investigated possible post-Apollo programs. NASA had tentative  plans to conduct unspecified orbital activities with Apollo systems, provision for which was included in the authorizations for the Apollo program One working group was set up to define the objectives and procedures for an Apollo Extension System (later designated Apollo Applications Program; still later, Skylab). Other groups were to study possibilities for a manned space station and a manned Mars landing.50
Biomedical input into advanced planning during this period (1963 to 1966) fell into three categories: biomedical specifications for an orbital laboratory, definition of biomedical experiments for advanced manned programs, and advanced human research. In October 1963, the NASA Office of Manned Space Flight set up a Biomedical Experiments Working Group to study the design and operational requirements and constraints which would be imposed upon a manned orbital laboratory by the incorporation" of biomedical experiments to measure the effects of prolonged weightlessness. 51 The group identified cardiovascular deconditioning and musculoskeletal catabolism as the "greatest potential problem areas" related to long-duration weightless flight. It recommended that NASA approach these problems on two levels. First, NASA should institute a broad and intensive program of ground-based biomedical research related to 18 different aspects of human physiology and performance, compiling precise measurements of such functions as defecation, excretion, and metabolism. These measurements should constitute the minimum safety package" that would be "integrated into any conceptual design." Second, these lines of research should be continued in flight. NASA should design the orbiting laboratory to include a physiology laboratory, a microscopy and chemistry laboratory, an x-ray facility, and a centrifuge and to accommodate "no fewer than four subjects," as this was considered the minimum number for orbiting valid biomedical data.52
The Office of Manned Space Flight established the Space Medicine Advisory Group in late 1963 to augment the work of the Biomedical Experiments Working Group. The advisory group was chaired by Dr. Sherman P. Vinograd, who was responsible for medical research within the office's Directorate of Space Medicine, but its members were drawn from biomedical research settings outside NASA. The initial purpose was to define the specific experiments that should be flown on an orbital laboratory. (Subsequently, the group was charged with reviewing and making recommendations concerning biomedical experiments proposals for Gemini and Apollo.) For the orbiting laboratory, the group designated 15 critical environmental factors: weightlessness, radiation, confinement, social restriction, monotony, threat of danger, artificial atmosphere, toxic substances, particulate matter, microorganisms, change in circadian rhythms, ultraviolet exposure, infrared exposure, noise, and thermal stress. It recommended the development of 14 experiments to measure the  combined effect of weightlessness and each of the other stress factors and 6 more experiments to evaluate the combined effect of weightlessness and combinations of the other factors. The report called for the laboratory to remain in orbit for at least one year and have a crew of 6 to 12 persons. It also recommended an intensive program of preliminary biomedical research. 53
In addition to these planning activities, NASA supported "fundamental and applied research in man's functions in relation to the space environment" with direct applicability to the design and engineering of spacecraft systems. Directed by the Office of Biotechnology and Human Research, this was an multidisciplinary undertaking in which man was viewed as a component of a man-machine system.54 Activities in this area fell into four broad categories. First, man-machine integration studies were concerned with "critical points of contact of man with his vehicle," that is, with the man-machine interfaces that "involve man's health, comfort, survival, observation, decision-making, integrative and manipulative skills" and the ways "in which man's limitations may affect this system." Research in this area focused on such matters as the relationship of cabin arrangements to mission performance and the information and control links between space capsule systems and the human operator. The second category, biotechnology, covered design and development of advanced life support systems (e.g., artificial gravity and closed ecological environmental systems) and extravehicular equipment for planetary exploration and repair of spacecraft systems. The third area, applied research on animals, addressed the potential hazards of advanced spaceflight. The final area of research centered on development of advanced bioinstrumentation.55 Although this research was directed toward problems related to manned spaceflight, the biotechnology and human research efforts were not conducted under the auspices of the approved manned space program; while the research was nominally applied in nature, its actual applications remained theoretical.
From 1962 to 1966 NASA's life sciences programs underwent major expansion and diversification. During the early years of Project Mercury, life sciences requirements were limited almost exclusively to medical operations, with very little research and development. By the end of the project, NASA's life sciences programs encompassed basic biomedical research and applied research and technology development as well as medical operations which expanded concurrently. In Mercury, the life sciences had a single objective contribute to ensuring human health, safety, and  performance in short-duration spaceflight. By the end of Mercury, the objectives included basic biological research; basic and applied medical research in support of both approved and advanced manned programs; planning of inflight biological and medical experiments; development, testing, and evaluation of life support and protective systems for approved manned flights; operational support for approved manned flights; and collection, reduction, and analysis of biomedical data obtained in fIight.
These expanded objectives, combined with the priorities of the manned lunar landing program, had important implications for the organization and management of life sciences programs. The life sciences had to be organized to support the lunar landing program while meeting a diversity of new obligations. Coordination had to be arranged among biologists, physicians, psychologists, and engineers. In-house capabilities for supporting these activities had to be provided. Finally, in meeting its new obligations in the life sciences, NASA had to generate support-or at least minimize opposition-from Congress, the military services, and the scientific community.